Predicting Kidney Damage from Chemotherapy for Mesothelioma

It may be possible to predict which mesothelioma patients are at risk for kidney damage from chemotherapy and take steps to prevent it. 

Japanese cancer researchers have linked a protein called megalin to cisplatin-related nephrotoxicity. 

Cisplatin is one of the main drugs used to treat mesothelioma. The researchers say people with more megalin in their urine are more likely to have kidney damage from chemotherapy with cisplatin. 

Kidney Damage is a Risk of Chemotherapy

Malignant mesothelioma is a rare cancer with no cure. Although scientists are working on other options, chemotherapy is the main treatment for mesothelioma. Most patients have a combination of Alimta (pemetrexed) and the platinum-based drug cisplatin.

One of the biggest risks with cisplatin is kidney damage from chemotherapy. Kidneys filter waste and toxins from the blood and release them as urine. The kidneys also help regulate blood pressure and calcium metabolism. 

If the kidneys do not work properly, water and waste build up. The body may swell and the patient may even end up in a coma. If the kidney damage is severe, a patient may have to have dialysis or a transplant. 

Megalin and its Role in Renal Function

Some mesothelioma patients experience kidney damage from chemotherapy while others do not. The Japanese study suggests that megalin might give doctors a way to predict which patients are which. 

Megalin is also called LRP2. It is a receptor protein on the membrane of certain epithelial cells, including those in the kidneys. Megalin helps regulate the uptake of other proteins and lipids.

Minimizing the Danger for At-Risk Patients

Forty-five patients with either lung cancer or pleural mesothelioma had urine tests before they started chemotherapy. Researchers compared the level of megalin in their urine to how well their kidneys worked after chemotherapy. 

“A negative correlation was found between baseline urinary A-megalin levels and change in eGFR [a measure of kidney function],” writes author Satoshi Shoji of Niigata University.

The higher the megalin level in the urine, the more likely a patient was to have kidney damage from chemotherapy. Patients in the top 25 percent of megalin levels had “significantly higher risk of eGFR decline” than those in the lowest 25 percent.

“This is the first report demonstrating that pre-chemotherapy urinary A-megalin levels are correlated with the development of cisplatin-induced nephrotoxicity,” concludes the report.

The authors say if doctors could identify at-risk patients, they might decide to try a different mesothelioma treatment. If they do go ahead with chemotherapy, they might be able to take steps to minimize the damage. 

Source:

Shoji, S, et al, “Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity: a prospective observational study”, December 2019, BMC Cancer, https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-6398-2